HLA class II antigen expression and the autoimmune thyroid response in patients with benign and malignant thyroid tumors

To further understand the relationship between the immune system and the neoplastic human thyroid cell we investigated the degree of intrathyroidal lymphocytic infiltration and thyroid HLA class II expression in 17 patients with thyroid tumors. In another 60 thyroid tumor patients the association of thyroidal lymphocytic infiltration with thyroid autoantibody production was analyzed. In total 117 thyroid tissues were examined including tissue obtained at autopsy (n = 28), fetal thyroid tissue (n = 4), thyroid samples obtained from areas distant from benign follicular adenomas (n = 5), and 80 abnormal thyroids including patients with benign (n = 53) or malignant (n = 24) thyroid tumors and Hashimoto's thyroiditis (n = 3). Normal adult and fetal thyroid tissue had no significant lymphocytic infiltration and no detectable HLA-DR, -DP, or -DQ antigens on their thyroid follicular epithelial cells. The degree of lymphocytic infiltration in the nonneoplastic thyroid tissue of thyroid glands with benign and malignant thyroid tumors varied considerably and correlated with the presence and titer of serum thyroid autoantibodies measured by sensitive ELISA techniques. However, all but one of the benign follicular adenomas had thyroid cells negative for HLA class II determinants despite the presence of infiltrating lymphocytes, while 7 of 10 thyroid carcinomas expressed class II antigen (principally HLA-DR) even when only minor degrees of lymphocytic infiltration were present. These data indicate a correlation between lymphocytic infiltrates and serum thyroid autoantibody titers but the relationship with HLA class II expression is more complex. Since we have previously shown that HLA class II antigen expression can be induced by local interferon-γ secretion, presumably from activated T cells, we conclude that estimates of simple thyroid lymphocytic infiltration and serum autoantibody secretion do not correlate with the degree of intrathyroidal T-cell activation. Furthermore, our observation of increased expression of HLA class II antigens in thyroid cancer suggests considerable cellular heterogeneity in susceptibility to HLA class II antigen induction in human thyroid disease.